An ongoing clinical trial was formulated to assess therapeutic efficacy of high dose oral amiodarone in patients with hypertrophic cardiomyopathy and refractory cardiac symptoms compared with standard pharmacologic agents and to characterize hemodynamic and left ventricular functional responses associated with amiodarone to help define mechanisms of action. Thusfar, 40 patients with refractory cardiac symptoms on standard medical therapies have been studied as inpatients on the Cardiology Service and have been seen as outpatients at 2 months, 6 months, and 1 year after instituting oral amiodarone treatment. After stopping medications for several days in the hospital, high dose oral amiodarone resulted in beneficial clinical responses (defined as at least a 50% improvement in exercise performance compared with no medication values and a decrease in cardiac symptoms by at least one functional class) in 68% of the patient group. During chronic lower dose outpatient amiodarone treatment, improvement was generally maintained (63% clinical responders); some patients manifested further symptom benefit, and in others symptoms were worse compared with higher dose acute treatment. As might be expected in this group of severely symptomatic patients unresponsive to standard pharmacologic therapy, many patients failed to experience maintained clinical benefit. Nonetheless, 45% of the total patient cohort are still receiving amiodarone for an average follow-up of 14 months and have continued to describe persistent improvement in symptoms. One half of all patients with left ventricular outflow tract obstruction who were deemed operative candidates prior to initiating amiodarone have experienced sufficient symptomatic improvement so that surgery could be deferred. From this ongoing clinical trial we conclude that high dose oral amiodarone improves exercise capacity and reduces cardiac symptoms in the majority of patients with hypertrophic cardiomyopathy who have been refractory to standard medical therapy and long-term clinical follow-up indicates a modest diminution in clinical efficacy although almost one half of all patients have continued treatment after the first year with continued symptomatic improvement.